3-D multi-faceted, nano-globular PAMAM dendritic skeleton is a highly significant polymer that offers applications in biomedical, industrial, environmental and agricultural fields. This is mainly due to its enhanced properties, including adjustable surface functionalities, biocompatibility, non-toxicity, high uniformity and reduced cytotoxicity, as well as its numerous internal cavities. This trait inspires further exploration and advancements in tailoring approaches. The implementation of deliberate strategic modifications in the morphological characteristics of PAMAM is crucial through chemical and biological interventions, in addition to its therapeutic advancements. Thus, the production of peripheral groups remains a prominent and highly advanced technique in molecular fabrication, aimed at boosting the potential of PAMAM conjugates. Currently, there exist numerous dendritic-hybrid materials, despite the widespread use of PAMAM-conjugated frameworks as drug delivery systems, which are well regarded for their efficacy in enhancing potency through the incorporation of surface functions. This paper provides a comprehensive review of recent progress in the design and assembly of various components of PAMAM conjugates, focusing on their unique formulations. The review encompasses synthetic methodologies, a thorough evaluation of their applicability, and an analysis of their potential functions in the context of Drug Delivery Systems (DDS) in the current period.

Chronic Kidney Disease (CKD) has become one of the major life-threatening conditions. Moringa seeds have been reported to exhibit renoprotective effects, with Niazimicin as its characteristic component.

To investigate the anti-renal injury effects of Niazimicin and its mixed micelles (N-M) that composed of monomethyl ether poly (ethylene glycol)-polycaprolactone (mPEG-PCL) and polyethylene glycolated chitosan (PEG-CS) on adenine-induced CKD mice.

PEG-CS was prepared via formaldehyde linkage method. The thin film dispersion method was employed for the preparation of N-M before it was characterized in vivo and in vitro. The anti-renal injury effects were evaluated by analyzing the serum levels of creatinine (Cr), p-Cresol sulphate (pCs), indole sulphate (IS) and hematoxylin-eosin (HE)-stained sections of hepatic and renal pathological tissues in CKD mice.

The N-M were spherical micelles of uniform size and highly dispersed with particle size of 42.94 ± 0.58 nm, encapsulation efficiency (EE) of 97.73 ± 2.33% and drug loading (DL) of 16.17 ± 0.28%, as well as good stability, and a very low critical micelle concentration (CMC) value of 0.00731 mg/mL. The N-M had a delayed-release effect and higher oral bioavailability compared to Niazimicin.

In CKD mice, Niazimicin exhibited an anti-renal injury effect, while the renoprotective effect of N-M was superior to that of Niazimicin.

Amphiphilic diblock copolymers are used in drug delivery systems for cancer treatments. However, these carriers suffer from lower drug loading capacity, poor water solubility, and non-targeted drug release. Here, we utilized a computational approach to analyze the effect of the functional groups of the hydrophobic block on the drug-polymer interactions. To design effective drug carriers, four different amphiphilic block copolymer micelles with distinct aromatic and heteroaromatic groups at the hydrophobic core were subjected to molecular dynamics simulations. The solvent-accessible surface area, water shell, hydrogen bonding, and radius of gyration of the simulated micelles were determined. Further, we assessed the interactions between the hydrophobic block and drug molecules using linear interaction energy and non-covalent interactions. The computational studies revealed that the micelles containing a novel poly(γ-2-methoxyfuran-ε-caprolactone) (PFuCL) hydrophobic block have the highest polymer-drug interactions. From these findings, we synthesized a novel amphiphilic poly(ethylene glycol)-b-poly(γ-2-methoxyfuran(ε-caprolactone)) (PEG-b-PFuCL) block copolymer using ring-opening polymerization of FuCL monomer. The polymer was self-assembled in aqueous media to form micelles. The aromatic segment of PEG-b-PFuCL micelles enhanced the doxorubicin (DOX) loading through non-covalent interactions, resulting in a 4.25 wt% drug-loading capacity. We also showed that the hydrolysis of the ester bond allowed a faster in vitro drug release at pH 5.0 compared to pH 7.4. Cell viability experiments revealed that DOX-loaded PEG-b-PFuCL micelles show that micelles are cytotoxic and readily uptaken into MDA-MB-231 cells. Therefore, furan-substituted micelles will be an ideal drug carrier with higher polymer-to-drug interactions, enhanced drug loading, and lower premature leakage.

The application of metal-organic frameworks (MOFs) as drug delivery systems with a high drug-loading capacity and targeted delivery is advancing rapidly. This study is the first to elucidate the mechanism of drug-loading in MOFs. It focused on the crucial role of solvents in drug-loading capacity. Ibuprofen, which is widely used as a nonsteroidal antiflammatory drug, was selected as a model drug. The drug-loading capacities of zeolitic imidazolate framework-8 (ZIF-8) and Universitetet i Oslo-66-NH2 (UiO-66-NH2) were investigated in various solvents. For ZIF-8, an increase in the solvent dipole moment corresponded to an increase in the drug-loading capacity. Intriguingly, the converse trend was observed for UiO-66-NH2. Therein, a decrease in the solvent dipole moment caused an increase in the drug-loading. These observations indicated that the solvent dipole moment plays a critical role in the drug-loading mechanism of the MOFs. Furthermore, Raman spectroscopy in the solvents with different polarities revealed significant variations in the molecular vibrations of ZIF-8 and UiO-66-NH2. It was indicated that in both the MOFs, the drug-loading amount increased in the solvents when the molecular vibrations of the MOF were constrained. This study revealed that the solvent plays a crucial role in the drug-loading in MOFs, and the polarity of the solvents contributes significantly to the molecular vibration of MOFs during drug-loading, thereby affecting the drug-loading capacity.

Conventional ocular drug delivery systems face challenges like rapid clearance, high dosages, low compliance, and poor bioavailability. A novel solution utilizes mucoadhesive polymers for controlled release, enhancing drug effectiveness while reducing dosages and frequency. Polymeric micelles, nanosized colloidal DDS, are set to modify drug delivery for challenging drugs mainly belonging to Biopharmaceutical Classification System class II (low solubility and high permeability), class III (high solubility and low permeability), and class IV (low solubility and low permeability). Micelles solubilize poorly soluble drugs, shielding them from degradation and macrophage uptake and extending drug action. Their small size enables them to breach ocular barriers, elevating therapeutic impact and bioavailability. This review explores polymeric micelles' potential in ocular drug delivery, covering their introduction, formulation, preparation, characterization, applications, recent progress, and challenges through critical analysis of all possible research communications so far. The review also scrutinizes the transition from lab to clinical use. Polymeric micelles revolutionize ocular drug delivery by surmounting limitations through enhanced solubilization, protection, and sustained release. This comprehensive review highlights their potential to improve ocular drug delivery practices.

Due to the straightforward single-step synthesis, amphiphilic gradient copoly(2-oxazoline)s are becoming more popular alternative to their block analogue for the development of next-generation drug delivery systems. Here, we investigated the influence of polymer architecture on the physiochemical and biological assessment of nanoformulations formed by the self-assembly of gradient copoly(2-oxazoline)s. Two different architectures were synthesized: hydrophilic-grad-hydrophobic (mono-gradient) and hydrophobic-grad-hydrophilic-grad-hydrophobic (di-gradient) which contained a hydrophilic monomer, 2-ethyl-2-oxazoline (EtOx) and a hydrophobic monomer, 2-phenyl-2-oxazoline (PhOx). Di-gradient copolymers self-assembled in the presence of a hydrophobic model drug, curcumin and formed monodispersed or slightly polydispersed nanoparticle solution. On the other hand, mono-gradient copolymers formed polydispersed nanoparticle solutions. Di-gradient copolymer was slightly more efficient to solubilize curcumin. Mono-gradient copolymer nanoparticle showed faster monomer chain exchange kinetics and comparatively less stability in the presence of serum albumin. At longer incubation times, faster drug release was observed from the mono-gradient copolymer nanoformulations. Cytotoxicity of free curcumin and curcumin loaded nanoparticles in cancer cell of U87 MG (human glioblastoma cell) was dose and time-dependent, whereby the significant cell death occurred after 48 h. Curcumin-loaded mono-gradient copolymer nanoparticles inhibited U87MG cancel cell growth to a large extent compared to the di-gradient copolymer nanoparticles.

Recent studies have demonstrated that antioxidants like lutein considerably lower the prevalence of age-related macular degeneration (AMD), which has been connected to blindness in numerous older adults. By halting oxidation, antioxidants reduce the damage that free radicals do. However, the short residence time, low stability, and poor solubility of lutein limit their ocular bioavailability following topical application. This study aimed to develop and characterize a micelle nanogel formulation for the ocular delivery of lutein. The micelle nanogel delivery system suggests a novel therapeutic strategy for administering ocular drugs due to its longer retention on the ocular surface, improved corneal permeability, and lowering the need for frequent administration. We developed a nanosized lutein micelle and incorporated it into a gel base to increase the solubility and ocular permeability. The micelle nanoformulation underwent evaluations like mean particle size, entrapment efficiency (EE), zeta potential, in vitro release investigations, ex vivo permeation tests, cell line studies, and Hen's egg test chorioallantoic membrane (HET-CAM). This nanoformulation exhibited favorable particle size (205.2 ± 15.36 nm), PDI (0.3 ± 0.20), and zeta potential (- 14.2 to + 11.3 mV) with 84.5 ± 1.75% entrapment efficiency. Fourier transform infrared spectroscopy confirmed compatibility, while TEM showed nanoscale spherical structures. F4 demonstrated effective corneal penetration, enhanced fibroblast viability, antioxidant activity (IC50: 55.11 µg/mL), and mild ocular irritancy and better wound healing properties. Based on the results, the formulations were proven safe and efficient for drug delivery to the eyes.

Herbal medicine harnesses the therapeutic properties of natural compounds, providing a sustainable approach to healthcare. Due to its limited aqueous solubility, therapeutic potential remains largely unexplored. The enhanced therapeutic potential of the herbal drug entails meticulous formulation and an effective drug delivery matrix. In this study, we formulated a hydrogel system based on Carboxymethylcellulose to deliver the herbal drug, J. adhatoda. The phytochemicals in the J. adhatoda extract involved in the crosslinking of the hydrogel via hydrogen bonding resulted from the interaction with the hydroxyl and carboxyl group of the polymeric chains, confirmed by the FT-IR studies. Rheological studies demonstrated improved mechanical properties with increasing extract concentration (20 μg to 100 μg), with yield stress increasing from 58.83 Pa to 121.5 Pa. The hydrogels exhibited significant antimicrobial activity, reducing biofilm formation against S. aureus, E. faecalis, E. coli, and K. pneumoniae by 71 %, 68 %, 61 %, and 57 %. Antioxidant activity improved with extract concentration, increasing from 29 % to 74 %. The optimal anticancer activity of the hydrogels showed IC50 values of 37.4 μL for MCF-7 and 65 μL for A431 cell lines. These findings demonstrate that J. adhatoda-impregnated CMC hydrogels offer enhanced bioactivity and mechanical strength, positioning them as promising candidates for biomedical applications.

Amphiphilic polymers form molecular monolayers at aqueous interfaces, stabilizing the discontinuity between two phases and acting as macromolecular surfactants. These polymer monolayers exhibit superior mechanical stability compared to traditional surfactants, making them useful in various applications, including structured liquids, drug delivery, lung surfactant therapy, protein encapsulation, extraction separation, and templates for synthesis. Despite their significance, the molecular-level understanding of the structure of polymer monolayers and their relationship to their physical properties remain obscure. Thus, understanding their structural behavior is crucial for controlling interfaces and tailoring system properties. At the air-water interface, polymer chains adopt two-dimensional (2D) Gaussian coil conformations, scalable by 2D-conformational polymer scaling theory and a few parameters such as temperature, surface concentration, and surface pressure (Π). Beyond a critical Π, polymer chains transition to 3D conformations, a critical but understudied phenomenon. This study investigated regioisomeric effects on these stereoscopic transitions using the poly(vinylpyridine) (PVP) polymer family. Despite sharing solubility parameters, steric differences in nitrogen positioning within the pyridine ring significantly influence solvation and stereoscopic conformational transitions. Alloying these regioisomeric polymers further enables fine-tuning of monolayer transitions and mechanical properties, providing deeper insights into the design and control of interfacial polymer systems.

The chemical structure of a delivery nanovehicle plays a pivotal role in determining the efficiency of drug delivery within the body. Leveraging the unique architecture of bottlebrush (BB) polymers-characterized by variations in backbone length, grafting density, and self-assembly morphology-offers a novel approach to understanding the influence of structural properties on biological behavior. In this study, developed a drug delivery system based on core-shell BB polymers synthesized using a "grafting-from" strategy. Comprehensive characterization techniques, including nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), and atomic force microscopy (AFM), employed to confirm the polymers' structure. The BB polymers evaluated as carriers for molecules with differing hydrophobicity profiles, namely Rhodamine B and Paclitaxel. These nanocarriers systematically assessed for drug loading efficiency and penetration capabilities, compared to conventional polymeric micelles (PM) formed from linear amphiphilic polymers. BB-based nanocarriers exhibited superior cellular uptake in both 2D and 3D cell culture models when compared to PM. Furthermore, analysis of drug distribution and particle penetration highlighted the profound influence of polymer morphology on biological interactions. These findings underscore the potential of unimolecular carriers with precisely defined structures as promising drug delivery platforms for a wide range of biomedical applications.

7-Aminoactinomycin D (7AAMD) is the fluorescent analogue of the anticancer drug actinomycin D (AMD). In order to overcome toxic side effects and enhanced bioavailability of 7AAMD, micellar drug carrier systems could be useful. We have used cationic (hexadecetyltrimethylammonium bromide [CTAB]), anionic (sodium dodecyl sulphate [SDS]) and non-ionic (t-octylphenoxypolyoxyethanol, Triton-X100 [TX 100]) surfactants to prepare micelle. We have explored the mechanism of the interaction of 7AAMD with micelles using steady-state and time-resolved fluorescence spectroscopy. Our results revealed that the Stokes' shift values of 7AAMD were decreased in all three micellar medium compared to that in the absence of any micelle. Thus, 7AAMD is localized in less polar microenvironment of micelles than bulk water. In addition, from the time-resolved fluorescence study of 7AAMD, we found that the relative contribution of the conformers of 7AAMD depended on the surfactant head group. Furthermore, acrylamide induced fluorescence quenching study shows differential accessibility of the quencher molecules towards 7AAMD depending on the ionic nature of the surfactant head group. In the presence of acrylamide, 7AAMD was expelled out from the non-ionic TX 100 micelle but not in CTAB and SDS micelle. Thus, our results are valuable to design new drug delivery system for AMD-like antitumor agents.

The nitrogen mustard alkylating agent chlorambucil (CBL) is a critical component of chemotherapeutic regimens used in the treatment of chronic lymphocytic leukemia. The cancer cell-killing actions of CBL are limited by glutathione (GSH) conjugation, a process catalyzed by the GSH transferase hGSTA1-1 that triggers CBL efflux from cells. In the cancer cell microenvironment, intracellular GSH levels are elevated to counterbalance oxidative stress generated due to the high glycolytic demand. As many chemotherapeutic drugs trigger cell death through mechanisms that depend on reactive oxygen species (ROS), antioxidant capacity in cancer cells also represents a barrier to anticancer therapies. Here, we demonstrate that a heightened GSH content in cancer cells can also be exploited for cell-selective drug delivery. We successfully synthesized a malononitrile conjugate terpyridine-based derivative L1, which specifically reacts with GSH in the presence of other biologically relevant amino acids including cysteine (Cys) and homocysteine (Hcy). The significant change in the electronic spectra of L1 in the presence of GSH confirmed GSH detection, which was further corroborated by density functional theory calculations. We next encapsulated CBL into L1-containing, anthracene-functionalized, and 10,12-pentacosadiynoic acid (PCDA)- and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)-based liposomes (Lip-CBL-L1). We established successful CBL encapsulation and release from L1-containing liposomes in GSH-enriched cancer cells in vitro. Both Lip-CBL-L1 and the L1-lacking Lip-CBL control displayed cell-killing activity. However, human triple-negative breast cancer cells MDAMB231, human lung cancer cells A549, and murine leukemic WEHI cells were more sensitive to the cytotoxic effects of Lip-CBL-L1 compared to the nonmalignant cells (AC16 and HEK293). Indeed, in these cancer cell lines, Lip-CBL-L1 induced greater ROS generation compared to that of Lip-CBL. Together, our results provide initial evidence of the feasibility of exploiting the unique oxidant environment of cancer cells for optimized drug delivery.

Synthetic vinyl polymers have long been recognized for their potential to be utilized in drug delivery, tissue engineering, and other biomedical applications. The synthetic control that chemists have over their structure and properties is unmatched, allowing vinyl polymer-based materials to be precisely engineered for a range of therapeutic applications. Yet, their lack of biodegradability compromises the biocompatibility of vinyl polymers and has held back their translation into clinically used treatments for disease thus far. In recent years, radical ring-opening polymerization (rROP) has emerged as a promising strategy to render synthetic vinyl polymers biodegradable and bioresorbable. While rROP has long been touted as a strategy for preparing biodegradable vinyl polymers for biomedical applications, the translation of rROP into clinically approved treatments for disease has not yet been realized. This review highlights the opportunities for leveraging rROP to render vinyl polymers biodegradable and unlock their potential for use in biomedical applications.

Biofilms are a well-known multifactorial virulence factor with a pivotal role in chronic bacterial infections. Their pathogenicity is determined by the combination of strain-specific mechanisms of virulence and the biofilm extracellular matrix (ECM) protecting the bacteria from the host immune defense and the action of antibacterials. The successful antibiofilm agents should combine antibacterial activity and good biocompatibility with the capacity to penetrate through the ECM. The objective of the study is the elaboration of biofilm-ECM-destructive drug delivery systems: mixed polymeric micelles (MPMs) based on a cationic poly(2-(dimethylamino)ethyl methacrylate)-b-poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA35-b-PCL70-b-PDMAEMA35) and a non-ionic poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO100-b-PPO65-b-PEO100) triblock copolymers, loaded with ciprofloxacin or azithromycin. The MPMs were applied on 24 h pre-formed biofilms of Escherichia coli and Pseudomonas aeruginosa (laboratory strains and clinical isolates). The results showed that the MPMs were able to destruct the biofilms, and the viability experiments supported drug delivery. The biofilm response to the MPMs loaded with the two antibiotics revealed two distinct patterns of action. These were registered on the level of both bacterial cell-structural alterations (demonstrated by scanning electron microscopy) and the interaction with host tissues (ex vivo biofilm infection model on skin samples with tests on nitric oxide and interleukin (IL)-17A production).

Click chemistry has become one of the most powerful construction tools in the field of organic chemistry, materials science, and polymer science, as it offers hassle-free platforms for the high-yielding synthesis of novel materials and easy functionalization strategies. The absence of harsh reaction conditions or complicated workup procedures allowed the rapid development of novel biofunctional polymeric materials, such as biopolymers, tailor-made polymer surfaces, stimulus-responsive polymers, etc. In this review, we discuss various types of click reactions─including azide-alkyne cycloadditions, nucleophilic and radical thiol click reactions, a range of cycloadditions (Diels-Alder, tetrazole, nitrile oxide, etc.), sulfur fluoride exchange (SuFEx) click reaction, and oxime-hydrazone click reactions─and their use for the formation and study of biofunctional polymers. Following that, we discuss state-of-the-art biological applications of "click"-biofunctionalized polymers, including both passive applications (e.g., biosensing and bioimaging) and "active" ones that aim to direct changes in biosystems, e.g., for drug delivery, antiviral action, and tissue engineering. In conclusion, we have outlined future directions and existing challenges of click-based polymers for medicinal chemistry and clinical applications.

Polymers with hemiacetal esters integrated in their backbone provide beneficial degradation profiles for (immuno-) drug delivery. However, their fast hydrolysis and low drug loading capacity have limited their applications so far. Therefore, this study focuses on the stability and loading capacity of hemiacetal ester polymers. The hydrophobicity of the micellar core has a tremendous effect on the hemiacetal ester stability. For that purpose, we introduce a new monomer with a phenyl moiety for stabilizing the micellar core and improving drug loading. The carrier functionality can further be expanded by post-polymerization modifications via activated ester groups at the polymer chain end. This allows for covalent dye labeling, which provides substantial insights into the polymers' in vitro performance. Flow cytometric analyses on RAW dual macrophages revealed intact micelles exhibiting significantly higher cellular uptake compared to degraded species, thus, highlighting the potential of end group functionalized poly(hemiacetal ester)s for (immuno)drug delivery purposes.

Despite the advent of novel therapeutics, the efficient delivery of antineoplastic drugs remains a challenge. Biodegradable polymeric micelles represent a promising frontier by offering enhanced drug solubility, tumor targeting, and controlled release profiles. However, the underlying dynamics governing the drug encapsulation and solvation within these micellar structures is still vague and poorly understood. In this study, we used amphiphilic poly(γ-benzyloxy-ε-caprolactone)-b-poly(γ-2-[2-(2-methoxy ethoxy)ethoxy]ethoxy-ε-caprolactone) as a model copolymer with doxorubicin as a model drug and performed all-atom molecular dynamics simulations to understand the regulating mechanism of the encapsulation process. The results are in good agreement with the experimental results. In addition, we interpreted the dynamic behavior of the polymeric micelles and vital intermolecular interactions that play a key role in drug encapsulation. Our study provides a theoretical approach to obtain insights for designing and enhancing novel anticancer drug carriers for therapeutics.

Albumin is a nature-derived, versatile protein carrier, that has been explored extensively by researchers for anticancer drug delivery due to its role in enhancing drug stability, solubility, circulation time, targeting capabilities, and overall therapeutic efficacy. Albumin nanoparticles possess inherent biocompatibility, biodegradability, and passive tumor-targeting ability due to the enhanced permeability and retention effect. However, non-specific accumulation of cytotoxic agents in healthy tissues remains a challenge. In this paper, the functionalization of albumin nanoparticles using various biomolecules including antibodies, nucleic acids, proteins and peptides, vitamins, chondroitin sulfate, hyaluronic acid, and lactobionic acid have been discussed which enables specific recognition and binding to cancer cells. Furthermore, we highlight the supremacy of such a targeted approach in tumor-specific drug delivery, minimization of off-target effects, potential improvement in therapeutic efficacy, cellular internalization, reduced side effects, and better clinical outcomes. This review centers on how they have revolutionized the field of biomedical research and tuned into an excellent targeted approach. In conclusion, this review highlights in detail the role of albumin as a nanocarrier for tumor-targeted delivery using biomolecules as ligands.

Surfactants and dioxins are increasingly being released into the environment due to their excessive usage and their improper disposal. These pollutants cause considerable harm to both humans and the natural environment. Therefore, their removal from water and wastewater, which form major pathways for their transmission, is necessary. Considerable research efforts have been devoted to finding a suitable method for the complete removal of these pollutants. The treatment options for both surfactants and dioxins could be similar but differ in terms of removal efficiencies for each. For example, surfactant removal through coagulation resulted in almost 68%, while for dioxins it attained 98% efficiency. Another method tested for the removal of surfactants is nanobubbling which recorded a 99% removal efficiency, while it was found to be inapplicable for the removal of dioxins due to the difference in the structure of the two products. Worth noting is that among the studied removal methods, biochar-based adsorption stands as one of the most promising techniques in terms of removal efficiency, cost, and sustainability covering the two pollutants. This review deals with the sources and impacts of these pollutants and discusses the recent developments in treatment methods, as compared to already-existing methods, for their elimination from water and wastewater, with the objective of highlighting the most sustainable methods for field application.

Electrical conductimetry and dynamic light scattering (DLS) were used to investigate the aggregation behaviors of four amino acid-based surfactants (AABSs; undecanoyl-glycine, undecanoyl-l-alanine, undecanoyl-l-valine, undecanoyl-l-leucine) in the presence of five linear diamine counterions (1,2-diaminoethane, 1,3-diaminopropane, 1,4-diaminobutane, 1,5-diaminopentane, 1,6-diaminohexane). Electrical conductimetry was used to measure the CMCs for each system, which ranged from 5.1 to 22.5 mM. With respect to counterions, the obtained CMCs decreased with increases in the interamine spacer length; this was attributed to the improved torsional binding flexibility in longer counterions. Strong linear correlations (mean R2 = 0.9443) were observed between the CMCs and predicted surfactant partition coefficients (logP; water/octanol), suggesting that micellization is primarily driven by the AABS's hydrophobicity for these systems. However, significant deviations in this linear relationship were observed for systems containing 1,2-diaminoethane, 1,4-diaminobutane, and 1,6-diaminohexane (p = 0.0774), suggesting altered binding dynamics for these counterions. pH measurements during the CMC determination experiments indicated the full deprotonation of the AABSs but did not give clear insights into the counterion protonation states, thus yielding an inconclusive evaluation of their charge stabilization effects during binding. However, DLS measurements revealed that the micellar size remained largely independent of the counterion length for counterions longer than 1,2-diaminoethane, with hydrodynamic diameters ranging from 2.2 to 2.8 nm. This was explained by the formation of charge-stabilized noncovalent dimers, with each counterion bearing a full +2 charge. Conductimetry-based estimates of the degrees of counterion binding (β) and free energies of micellization (ΔG°M) revealed that bulky AABSs exhibit preferential binding to counterions with an even number of methylene groups. It is proposed that when these counterions form noncovalent dimers, perturbations in their natural geometries result in the formation of a binding pocket that accommodates the AABS steric bulk. While the direct application of these systems remains to be seen, this study provides valuable insights into the structure-property relationships that govern AABS aggregation.

Drug-loaded polymeric micelles have proven to be highly effective carrier systems for the efficient delivery of hydrophobic photosensitizers (PSs) in photodynamic therapy (PDT). This study introduces the micellization potential of poly(oligoethylene glycol methyl ether methacrylate) (pOEGMA) as a novel approach, utilizing the hydrophobic methacrylate segments of pOEGMA to interact with highly hydrophobic zinc phthalocyanine (ZnPc), thereby forming a potential micellar drug carrier system. The ZnPc molecule was synthesized from phthalonitrile derivatives and its fluorescence, photodegradation, and singlet oxygen quantum yields were determined in various solvents. In solvents such as tetrahydrofuran, dimethyl sulfoxide, and N,N-dimethylformamide, the ZnPc compound exhibited the requisite photophysical and photochemical properties for PDT applications. The pOEGMA homopolymer was synthesized via reversible addition-fragmentation chain-transfer polymerization, while ZnPc-loaded pOEGMA micelles were prepared using the nanoprecipitation method. Characterization of the pOEGMA, ZnPc, and micelles was conducted using FTIR,1H-NMR, dynamic light scattering, matrix-assisted laser desorption/ionization time-of-flight mass spectrometries, gel permeation chromatography, and transmission electron microscopy. The critical micelle concentration was determined to be 0.027 mg ml-1using fluorescence spectrometry. The drug loading and encapsulation efficiencies of the ZnPc-loaded micelles were calculated to be 0.67% and 0.47%, respectively. Additionally, the release performance of ZnPc from pOEGMA micelles was monitored over a period of nearly 10 d, while the lyophilized micelles exhibited stability for 3 months. Lastly, the ZnPc-loaded micelles were more biocompatible than ZnPc on L929 cell line. The results suggest that the pOEGMA homopolymer possesses the capability to micellize through its methacrylate segments when interacting with highly hydrophobic molecules, presenting a promising avenue for enhancing the delivery efficiency of hydrophobic PSs in PDT. Moreover, it was also deciphered that obtained formulations were highly biocompatible according to cytotoxicity results and could be safely employed as drug delivery systems in further applications.

The design of novel drug delivery systems is exceptionally critical in disease treatments. Among the existing drug delivery systems, mesoporous silica nanoparticles (MSNs) have shown profuse promise owing to their structural stability, tunable morphologies/sizes, and ability to load different payload chemistry. Significantly, the presence of surface silanol groups enables functionalization with relevant drugs, imaging, and targeting agents, promoting their utility and popularity among researchers. Stimuli-responsive silanol conjugates have been developed as a novel, more effective way to conjugate, deliver, and release therapeutic drugs on demand and precisely to the selected location. Therefore, it is urgent to summarize the current understanding and the surface silanols' role in making MSN a versatile drug delivery platform. This review provides an analytical understanding of the surface silanols, chemistry, identification methods, and their property-performance correlation. The chemistry involved in converting surface silanols to a stimuli-responsive silica delivery system by endogenous/exogenous stimuli, including pH, redox potential, temperature, and hypoxia, is discussed in depth. Different chemistries for converting surface silanols to stimuli-responsive bonds are discussed in the context of drug delivery. The critical discussion is culminated by outlining the challenges in identifying silanols' role and overcoming the limitations in synthesizing stimuli-responsive mesoporous silica-based drug delivery systems.

The pulmonary drug delivery system is a promising and evolving technology in which the prescribed medicine is breathed through the lungs, and subsequently, it enters the circulation via the alveolar epithelium. This category of pulmonary drug delivery system is an appealing and non-invasive administration method. Pulmonary drug delivery is most commonly utilized to treat airway problems by providing locally active medicines directly to their site of action. The dose required to have a pharmacological effect is reduced when medicines are delivered directly to their site of action. In addition to locally acting medications, the pulmonary route can be utilized to deliver compounds with systemic effects, such as in the case of insulin inhalation therapy for systemic absorption. Particle size, bioavailability, device compatibility, and other aspects must be addressed, including the formulation of drugs into an acceptable dosage for inhalation with sufficient stability. This formulation must also be used in conjunction with a suitable inhaler device that produces an aerosol with a particle or droplet size that assures deposition in the required targeted area of the pulmonary system. Recent advancements in pulmonary drug delivery include the development of targeted nanoparticles and inhalable biologics, which enhance drug absorption and efficacy while minimizing systemic side effects. Future directions focus on personalized medicine approaches and advanced inhalation technologies, although limitations such as variable patient adherence and the need for precise dosing continue to pose challenges.

Cardiac arrhythmia, a disorder of abnormal electrical activity of the heart that disturbs the rhythm of the heart, thereby affecting its normal function, is one of the leading causes of death from heart disease worldwide and causes millions of deaths each year. Currently, treatments for arrhythmia include drug therapy, radiofrequency ablation, cardiovascular implantable electronic devices (CIEDs), including pacemakers, defibrillators, and cardiac resynchronization therapy (CRT). However, these traditional treatments have several limitations, such as the side effects of medication, the risks of device implantation, and the complications of invasive surgery. Nanotechnology and nanomaterials provide safer, effective and crucial treatments to improve the quality of life of patients with cardiac arrhythmia. The large specific surface area, controlled physical and chemical properties, and good biocompatibility of nanobiomaterials make them promising for a wide range of applications, such as cardiovascular drug delivery, tissue engineering, and the diagnosis and therapeutic treatment of diseases. However, issues related to the genotoxicity, cytotoxicity and immunogenicity of nanomaterials remain and require careful consideration. In this review, we first provide a brief overview of cardiac electrophysiology, arrhythmia and current treatments for arrhythmia and discuss the potential applications of nanobiomaterials before focusing on the promising applications of nanobiomaterials in drug delivery and cardiac tissue repair. An in-depth study of the application of nanobiomaterials is expected to provide safer and more effective therapeutic options for patients with cardiac arrhythmia, thereby improving their quality of life.

Prostate cancer (PC) is the third most common male cancer in the world, which occurs due to various mutations leading to the loss of chromatin structure. There are multiple treatments for this type of cancer, of which chemotherapy is one of the most important. Sometimes, a combination of different treatments, such as chemotherapy, radiotherapy, and surgery, are used to prevent tumor recurrence. Among other treatments, androgen deprivation therapy (ADT) can be mentioned, which has had promising results. One of the drawbacks of chemotherapy and ADT treatments is that they are not targeted to the tumor tissue. For this reason, their use can cause extensive side effects. Treatments based on nanomaterials, known as nanomedicine, have attracted much attention today. Nanoparticles (NPs) are one of the main branches of nanomedicine, and they can be made of different materials such as polymer, metal, and carbon, each of which has distinct characteristics. In addition to NPs, nanovesicles (NVs) also have therapeutic applications in PC. In treating PC, synthetic NVs (liposomes, micelles, and nanobubbles) or produced from cells (exosomes) can be used. In addition to the role that NPs and NVs have in treating PC, due to being targeted, they can be used to diagnose PC and check the treatment process. Knowing the characteristics of nanomedicine-based treatments can help design new treatments and improve researchers' understanding of tumor biology and its rapid diagnosis. In this study, we will discuss conventional and nanomedicine-based treatments. The results of these studies show that the use of NPs and NVs in combination with conventional treatments has higher efficacy in tumor treatment than the individual use of each of them.

The rise of antibiotic resistance poses a significant threat to public health worldwide, leading researchers to explore novel solutions to combat this growing problem. Nanotechnology, which involves manipulating materials at the nanoscale, has emerged as a promising avenue for developing novel strategies to combat antibiotic resistance. This cutting-edge technology has gained momentum in the medical field by offering a new approach to combating infectious diseases. Nanomaterial-based therapies hold significant potential in treating difficult bacterial infections by circumventing established drug resistance mechanisms. Moreover, their small size and unique physical properties enable them to effectively target biofilms, which are commonly linked to resistance development. By leveraging these advantages, nanomaterials present a viable solution to enhance the effectiveness of existing antibiotics or even create entirely new antibacterial mechanisms. This review article explores the current landscape of antibiotic resistance and underscores the pivotal role that nanotechnology plays in augmenting the efficacy of traditional antibiotics. Furthermore, it addresses the challenges and opportunities within the realm of nanotechnology for combating antibiotic resistance, while also outlining future research directions in this critical area. Overall, this comprehensive review articulates the potential of nanotechnology in addressing the urgent public health concern of antibiotic resistance, highlighting its transformative capabilities in healthcare.

Block copolymer micelles, formed by the self-assembly of amphiphilic polymers, address formulation challenges, such as poor drug solubility and permeability. These micelles offer advantages including a smaller size, easier preparation, sterilization, and superior solubilization, compared with other nanocarriers. Preclinical studies have shown promising results, advancing them toward clinical trials. Their mucoadhesive properties enhance and prolong contact with the ocular surface, and their small size allows deeper penetration through tissues, such as the cornea. Additionally, copolymeric micelles improve the solubility and stability of hydrophobic drugs, sustain drug release, and allow for surface modifications to enhance biocompatibility. Despite these benefits, long-term stability remains a challenge. In this review, we highlight the preclinical performance, structural frameworks, preparation techniques, physicochemical properties, current developments, and prospects of block copolymer micelles as ocular drug delivery systems.

One of the key aspects of coping efficiently with complex pathological conditions is delivering the desired therapeutic compounds with precision in both space and time. Therefore, the focus on nuclear-targeted delivery systems has emerged as a promising strategy with high potential, particularly in gene therapy and cancer treatment. Here, we explore the design of supramolecular nanoassemblies as vehicles to deliver specific compounds to the nucleus, with the special focus on polymer and peptide-based carriers that expose nuclear localization signals. Such nanoassemblies aim at maximizing the concentration of genetic and therapeutic agents within the nucleus, thereby optimizing treatment outcomes while minimizing off-target effects. A complex scenario of conditions, including cellular uptake, endosomal escape, and nuclear translocation, requires fine tuning of the nanocarriers' properties. First, we introduce the principles of nuclear import and the role of nuclear pore complexes that reveal strategies for targeting nanosystems to the nucleus. Then, we provide an overview of cargoes that rely on nuclear localization for optimal activity as their integrity and accumulation are crucial parameters to consider when designing a suitable delivery system. Considering that they are in their early stages of research, we present various cargo-loaded peptide- and polymer nanoassemblies that promote nuclear targeting, emphasizing their potential to enhance therapeutic response. Finally, we briefly discuss further advancements for more precise and effective nuclear delivery.

A series of amphiphilic block copolymer (BCP) micelles based on poly(dimethylsiloxane) (PDMS) and poly(ethylene glycol) (PEG) were synthesized by a one-step reaction in the presence of tris(pentafluorophenyl)borane (BCF) as a catalyst. The structural composition of PDMS-b-PEG (PR11) and PEG-b-PDMS-b-PEG (PR12) was corroborated by FTIR, 29Si NMR, and TGA. The BCPs were assembled in an aqueous solution, obtaining micelles between 57 and 87 nm in size. PR11 exhibited a higher (2.0 g L-1) critical micelle concentration (CMC) than PR12 (1.5 g L-1) due to the short chain length. The synthesized nano micelles were used to encapsulate curcumin, which is one of three compounds of turmeric plant 'Curcuma longa' with significant biological activities, including antioxidant, chemoprotective, antibacterial, anti-inflammatory, antiviral, and anti-depressant properties. The encapsulation efficiency of curcumin was 60% for PR11 and 45% for PR12. Regarding the release study, PR11 delivered 53% curcumin after five days under acidic conditions (pH of 1.2) compared to 43% at a pH of 7.4. The degradation products of curcumin were observed under basic conditions and were more stable at acidic pH. In both situations, the release process is carried out by breaking the silyl-ether bond, allowing the release of curcumin. PR11 showed prolonged release times, so it could be used to reduce ingestion times and simultaneously work as a nanocarrier for other hydrophobic drugs.

Skin carcinoma is one of the most prevalent types of carcinomas. Due to high incidence of side effects in conventional therapies (radiotherapy and chemotherapy), photodynamic therapy (PDT) has gained huge attention as an alternate treatment strategy. PDT involves the administration of photosensitizers (PS) to carcinoma cells which produce reactive oxygen species (ROS) on irradiation by specific wavelengths of light that result in cancer cells' death via apoptosis, autophagy, or necrosis. Topical delivery of PS to the skin cancer cells at the required concentration is a challenge due to the compounds' innate physicochemical characteristics. Nanocarriers have been observed to improve skin permeability and enhance the therapeutic efficiency of PDT. Polymeric nanoparticles (NPs), metallic NPs, and lipid nanocarriers have been reported to carry PS successfully with minimal side effects and high effectiveness in both melanoma and non-melanoma skin cancers. Advanced carriers such as quantum dots, microneedles, and cubosomes have also been addressed with reported studies to show their scope of use in PDT-assisted skin cancer treatment. In this review, nanocarrier-aided PDT in skin cancer therapies has been discussed with clinical trials and patents. Additionally, novel nanocarriers that are being investigated in PDT are also covered with their future prospects in skin carcinoma treatment.

High glutathione production is known to be one of the defense mechanisms by which many cancer cells survive elevated oxidative stress. By explicitly targeting glutathione in these cancer cells and diminishing its levels, oxidative stress can be intensified, ultimately triggering apoptosis or programmed cell death. Herein, we developed a novel approach by creating maleimide-functionalized polycaprolactone polymers, specifically using 2,3-diiodomaleimide functionality to reduce the level of glutathione in cancer cells. Polycaprolactone was chosen to conjugate the 2,3-diiodomaleimide functionality due to its biodegradable and biocompatible properties. The amphiphilic block copolymer was synthesized using PEG as a macroinitiator to make corresponding polymeric micelles. The resulting 2,3-diiodomaleimide-conjugated polycaprolactone micelles effectively quenched glutathione, even at low concentrations (0.01 mg mL-1). Furthermore, we loaded these micelles with the anticancer drug doxorubicin (DOX), which exhibited pH-dependent drug release. We obtained a loading capacity (LC) of 3.5% for the micelles, one of the highest LC reported among functional PCL-based micelles. Moreover, the enhanced LC doesn't affect their release profile. Cytotoxicity experiments demonstrated that empty and DOX-loaded micelles inhibited cancer cell growth, with the DOX-loaded micelles displaying the highest cytotoxicity. The ability of the polymer to quench intracellular GSH was also confirmed. This approach of attaching maleimide to polycaprolactone polymers shows promise in depleting elevated glutathione levels in cancer cells, potentially improving cancer treatment efficacy.

There is a myriad of diseases that plague the world ranging from infectious, cancer and other chronic diseases with varying interventions. However, the dynamism of causative agents of infectious diseases and incessant mutations accompanying other forms of chronic diseases like cancer, have worsened the treatment outcomes. These factors often lead to treatment failure via different drug resistance mechanisms. More so, the cost of developing newer drugs is huge. This underscores the need for a paradigm shift in the drug delivery approach in order to achieve desired treatment outcomes. There is intensified research in nanomedicine, which has shown promises in improving the therapeutic outcome of drugs at preclinical stages with increased efficacy and reduced toxicity. Regardless of the huge benefits of nanotechnology in drug delivery, challenges such as regulatory approval, scalability, cost implication and potential toxicity must be addressed via streamlining of regulatory hurdles and increased research funding. In conclusion, the idea of nanotechnology in drug delivery holds immense promise for optimizing therapeutic outcomes. This work presents opportunities to revolutionize treatment strategies, providing expert opinions on translating the huge amount of research in nanomedicine into clinical benefits for patients with resistant infections and cancer.

Breast cancer continues to pose a substantial global health challenge, emphasizing the critical need for the advancement of novel therapeutic approaches. Key players in the regulation of apoptosis, a fundamental process in cell death, are the B-cell lymphoma 2 (Bcl-2) family proteins, namely Bcl-2 and Bax. These proteins have garnered attention as highly promising targets for the treatment of breast cancer. Targeting the overexpressed anti-apoptotic Bcl-2 protein in breast cancer, Gefitinib (GEF), an EGFR (Epidermal Growth Factor Receptor) inhibitor, emerges as a potential solution. This study focuses on designing Gefitinib-loaded polymeric mixed micelles (GPMM) using poloxamer 407 and TPGS (D-alpha tocopherol PEG1000 succinate) for breast cancer therapy. In silico analyses unveil strong interactions between GEF- Bcl-2 and TPGS-Pgp-2 receptors, indicating efficacy against breast cancer. Molecular dynamics simulations offer insights into GEF and TPGS interactions within the micelles. Formulation optimization via Design of Experiment ensures particle size and entrapment efficiency within acceptable ranges. Characterization tools such as zeta sizer, ATR-FTIR, XRD, TEM, AFM, NMR, TGA, and DSC confirms particle size, structure, functional groups, and thermodynamic events. The optimized micelles exhibit a particle size of 22.34 ± 0.18 nm, PDI of 0.038 ± 0.009, and zeta potential of -0.772 ± 0.12 mV. HPLC determines 95.67 ± 0.34% entrapment efficiency and 1.05 ± 0.12% drug loading capacity. In-vitro studies with MDA-MB-231 cell lines demonstrate enhanced cytotoxicity of GPMM compared to free GEF, suggesting its potential in breast cancer therapy. Cell cycle analysis reveals apoptosis induction through key apoptotic proteins. Western blot results confirm GPMM's ability to trigger apoptosis in MDA-MB-231 cells by activating caspase-3, Bax, Bcl-2, and Parp. In conclusion, these polymeric mixed micelles show promise in selectively targeting cancer cells, warranting future in-vivo studies for optimized clinical application against breast cancer.

Myocardial infarction (MI) is one of the most prevalent types of cardiovascular disease. During MI, myocardial cells become ischemic and necrotic due to inadequate blood perfusion, leading to irreversible damage to the heart. Despite the development of therapeutic strategies for the prevention and treatment of MI, their effects are still unsatisfactory. Nanoparticles represent a new strategy for the pre-treatment and treatment of MI, and novel multifunctional nanoparticles with preventive and therapeutic capabilities hold promise for the prevention and treatment of this disease. This review summarizes the common types and properties of nanoparticles, and focuses on the research progress of nanoparticles for the prevention and treatment of MI.

Glipizide; an insulin secretagogue belonging to the sulfonylurea class, is a widely used antidiabetic drug for managing type 2 diabetes. However, the need for life-long administration and repeated doses poses challenges in maintaining optimal blood glucose levels. In this regard, orally active sustained-release nano-formulations can be a better alternative to traditional antidiabetic formulations. The present study explored an innovative approach by formulating orally active sustained-release nano-micelles using the amphiphilic lauric acid-conjugated-F127 (LAF127) block copolymer. LAF127 block copolymer was synthesized through esterification and thoroughly characterized before being employed to develop glipizide-loaded nano-micelles (GNM) via the thin-film hydration technique. The optimized formulation exhibited mean particle size of 341.40 ± 3.21 nm and depicted homogeneous particle size distribution with a polydispersity index (PDI) < 0.2. The formulation revealed a surface charge of -17.11 ± 6.23 mV. The in vitro release studies of glipizide from developed formulation depicted a sustained release profile. Drug loaded micelles exhibited a substantial reduction in blood glucose levels in diabetic rats for a duration of up to 24 h. Notably, neither the blank nano-micelles of LAF127 nor the drug loaded micelles manifested any indications of toxicity in healthy rats. This study provides an insight on suitability of synthesized LAF127 block copolymer for development of effective oral drug delivery systems for anti-diabetic activity without any significant adverse effects.

Fabrication of stimuli-responsive superstructure capable of delivering chemotherapeutics directly to the cancer cell by sparing healthy cells is crucial. Herein, we developed redox-responsive hollow spherical assemblies through self-assembly of disulfide-linked cysteine-diphenylalanine (SN). These fluorescent hollow spheres display intrinsic green fluorescence, are proteolytically stable and biocompatible, and allow for real-time monitoring of their intracellular entry. The disulfide bond facilitates selective degradation in the presence of high glutathione (GSH) concentrations, prevalent in cancer cells. We achieved efficient encapsulation (68.72%) of the anticancer drug doxorubicin (Dox) and demonstrated GSH-dependent, redox-responsive drug release within cancerous cells. SN-Dox exhibited a 20-fold lower effective concentration (2.5 μM) for compromising breast cancer cell viability compared to non-malignant cells (50 μM). The ability of SN-Dox to initiate DNA damage signaling and trigger apoptosis was comparable to that of the unencapsulated drug. Our findings highlight the potential of SN for creating site-specific drug delivery vehicles for sustained therapeutic release.

Designing targeted drug delivery systems to effectively treat bone diseases ranging from osteoporosis to nonunion bone defects remains a significant challenge. Previously, nanoparticles (NPs) self-assembled from diblock copolymers of poly(styrene-alt-maleic anhydride)-b-poly(styrene) (PSMA-b-PS) delivering a Wnt agonist were shown to effectively target bone and improve healing via the introduction of a peptide with high affinity to tartrate-resistant acid phosphatase (TRAP), an enzyme deposited by the osteoclasts during bone remodeling. Despite these promising results, the underlying biological factors governing targeting and subsequent drug delivery system (DDS) design parameters have not been examined to enable the rational design to improve bone selectivity. Therefore, this work investigated the effect of target ligand density, the treatment window after injury, specificity of TRAP binding peptide (TBP), the extent of TRAP deposition, and underlying genetic factors (e.g., mouse strain differences) on TBP-NP targeting. Data based on in vitro binding studies and in vivo biodistribution analyses using a murine femoral fracture model suggest that TBP-NP-TRAP interactions and TBP-NP bone accumulation were ligand-density-dependent; in vitro, TRAP affinity was correlated with ligand density up to the maximum of 200,000 TBP ligands/NP, while NPs with 80,000 TBP ligands showed 2-fold increase in fracture accumulation at day 21 post injury compared with that of untargeted or scrambled controls. While fracture accumulation exhibited similar trends when injected at day 3 compared to that at day 21 postfracture, there were no significant differences observed between TBP-functionalized and control NPs, possibly due to saturation of TRAP by NPs at day 3. Leveraging a calcium-depletion diet, TRAP deposition and TBP-NP bone accumulation were positively correlated, confirming that TRAP-TBP binding leads to TBP-NP bone accumulation in vivo. Furthermore, TBP-NP exhibited similar bone accumulation in both C57BL/6 and BALB/c mouse strains versus control NPs, suggesting the broad applicability of TBP-NP regardless of the underlying genetic differences. These studies provide insight into TBP-NP design, mechanism, and therapeutic windows, which inform NP design and treatment strategies for fractures and other bone-associated diseases that leverage TRAP, such as marrow-related hematologic diseases.

Stimuli-responsive amphiphilic polymers are known to be precursors to forming promising nanoarchitectonics with tunable properties for application in biomedical sciences. Currently, self-immolative polymers are widely recognized as an emerging class of responsive materials with excellent degradability, which is one of the crucial criteria for designing a robust drug delivery vehicle. Here, we design an amphiphilic polyurethane endowed with a redox-responsive self-immolative linker and a pH-responsive tertiary amine on the backbone, which forms entropy-driven nanoscale supramolecular assemblies (average hydrodynamic diameter ∼110 nm) and is programmed to disassemble in a redox environment (GSH) due to the degradation of the polymer in a self-immolative fashion. The nanoassembly shows efficient drug sequestration and release in a controlled manner in response to glutathione (10 mM). The tertiary amine residing on the surface of the nanoassembly becomes protonated in the tumor microenvironment (pH ∼ 6.4-6.8) and generates positively charged nanoassembly (ζ-potential = +36 mV), which enhances the cancer cell-selective cellular uptake. The biological evaluation of the drug-loaded nanoassembly revealed triple-negative breast cancer (MDAMB-231) selective internalization and cell death while shielding normal cells (RBCs or PBMCs) from off-targeting toxicity. We envision that polyurethane with a redox-responsive self-immolative linker might open up new opportunities for a completely degradable polyurethane-based nanocarrier for drug delivery and diagnosis applications.

Micelle sizes are critical for a range of applications where the simple ability to adjust and lock in specific stable sizes has remained largely elusive. While micelle swelling agents are well-known, their dynamic re-equilibration in solution implies limited stability. Here, a non-equilibrium processing sequence is studied where supersaturated homopolymer swelling is combined with glassy-core ("persistent") micelles. This path-dependent process was found to sensitively depend on unimer concentration as revealed by DLS, SAXS, and TEM analysis. Here, lower-selectivity solvent combinations led to the formation of unimer-homopolymer aggregates and eventual precipitation, reminiscent of anomalous micellization. In contrast, higher-selectivity solvents enabled supersaturated homopolymer loadings favored by rapid homopolymer insertion. The demonstrated ∼40-130 nm core-size tuning exceeded prior equilibrium demonstrations and subsequent core-vitrification enabled size persistence beyond 6 months. Lastly, the linear change in micelle diameter with homopolymer addition was found to correlate with a plateau in the interfacial area per copolymer chain.

In addition to their classical role in ATP generation, mitochondria also contribute to Ca2+ buffering, free radical production, and initiation of programmed cell death. Mitochondrial dysfunction has been linked to several leading causes of morbidity and mortality worldwide including neurodegenerative, metabolic, and cardiovascular diseases as well as several cancer subtypes. Thus, there is growing interest in developing drug-delivery vehicles capable of shuttling therapeutics directly to the mitochondria. Here, we functionalized the conventional 10,12-pentacosadiynoic acid/1,2-dimyristoyl-sn-glycero-3-phosphocholine (PCDA/DMPC)-based liposome with a mitochondria-targeting triphenylphosphonium (TPP) cationic group. A fluorescent dansyl dye (DAN) group was also included for tracking mitochondrial drug uptake. The resultant PCDA-TPP and PCDA-DAN conjugates were incorporated into a 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)-based lipid bilayer, and these modified liposomes (Lip-DT) were studied for their cellular toxicity, mitochondrial targeting ability, and efficacy in delivering the drug Doxorubicin (Dox) to human colorectal carcinoma (HCT116) and human breast (MCF7) cancer cells in vitro. This Lip-DT-Dox exhibited the ability to shuttle the encapsulated drug to the mitochondria of cancer cells and triggered oxidative stress, mitochondrial dysfunction, and apoptosis. The ability of Lip-DT-Dox to trigger cellular toxicity in both HCT116 and MCF7 cancer cells was comparable to the known cell-killing actions of the unencapsulated drug (Dox). The findings in this study reveal a promising approach where conventional liposome-based drug delivery systems can be rendered mitochondria-specific by incorporating well-known mitochondriotropic moieties onto the surface of the liposome.

Prostate cancer is among the most common malignancies for men, with limited therapy options for last stages of the tumor. There are some different options for treatment and control of prostate tumor growth. However, targeting some specific molecules and cells within tumors has been attracted interests in recent years. The tumor microenvironment (TME) has an important role in the initiation of various malignancies, which can also expand the progression of tumor and facilitate invasion of malignant cells. By regulating immune responses and distinct changes in the metabolism of cells in the tumor, TME has substantial effects in the resistance of cancer cells to therapy. TME in various solid cancers like prostate cancer includes various cells, including cancer cells, supportive stromal cells, immunosuppressive cells, and anticancer inflammatory cells. Natural products including herbal-derived agents and also other natural compounds have been well studied for their anti-tumor potentials. These compounds may modulate various signaling pathways involved in TME, such as immune responses, the metabolism of cells, epigenetics, angiogenesis, and extracellular matrix (ECM). This paper provides a review of the current knowledge of prostate TME and complex interactions in this environment. Additionally, the potential use of natural products and also nanoparticles loaded with natural products as therapeutic adjuvants on different cells and therapeutic targets within prostate TME will be discussed.

Stimuli responsive delivery systems, also known as smart/intelligent drug delivery systems, are specialized delivery vehicles designed to provide spatiotemporal control over drug release at target sites in various diseased conditions, including tumor, inflammation and many others. Recent advances in the design and development of a wide variety of stimuli-responsive (pH, redox, enzyme, temperature) materials have resulted in their widespread use in drug delivery and tissue engineering. The aim of this review is to provide an insight of recent nanoparticulate drug delivery systems including polymeric nanoparticles, dendrimers, lipid-based nanoparticles and the design of new polymer-drug conjugates (PDCs), with a major emphasis on natural along with synthetic commercial polymers used in their construction. Special focus has been placed on stimuli-responsive polymeric materials, their preparation methods, and the design of novel single and multiple stimuli-responsive materials that can provide controlled drug release in response a specific stimulus. These stimuli-sensitive drug nanoparticulate systems have exhibited varying degrees of substitution with enhanced in vitro/in vivo release. However, in an attempt to further increase drug release, new dual and multi-stimuli based natural polymeric nanocarriers have been investigated which respond to a mixture of two or more signals and are awaiting clinical trials. The translation of biopolymeric directed stimuli-sensitive drug delivery systems in clinic demands a thorough knowledge of its mechanism and drug release pattern in order to produce affordable and patient friendly products.

Adamantane, a staple in medicinal chemistry, recently became a cornerstone of a supramolecular host-guest drug delivery system, ADA/CB[n]. Owing to a good fit between the adamantane cage and the host cavity of the cucurbit[n]uril macrocycle, formed strong inclusion complexes find applications in drug delivery and controlled drug release. Note that the cucurbit[n]uril host is not solely a delivery vehicle of the ADA/CB[n] system but rather influences the bioactivity and bioavailability of drug molecules and can tune drug properties. Namely, as host-guest interactions are capable of changing the intrinsic properties of the guest molecule, inclusion complexes can become more soluble, bioavailable and more resistant to metabolic conditions compared to individual non-complexed molecules. Such synergistic effects have implications for practical bioapplicability of this complex system and provide a new viewpoint to therapy, beyond the traditional single drug molecule approach. By achieving a balance between guest encapsulation and release, the ADA/CB[n] system has also found use beyond just drug delivery, in fields like bioanalytics, sensing assays, bioimaging, etc. Thus, chemosensing in physiological conditions, indicator displacement assays, in vivo diagnostics and hybrid nanostructures are just some recent examples of the ADA/CB[n] applicability, be it for displacements purposes or as cargo vehicles.

Iminoboronates and diazaborines are related classes of compounds that feature an imine ortho to an arylboronic acid (iminoboronate) or a hydrazone that cyclizes with an ortho arylboronic acid (diazaborine). Rather than acting as independent chemical motifs, the arylboronic acid impacts the rate of imine/hydrazone formation, hydrolysis, and exchange with competing nucleophiles. Increasing evidence has shown that the imine/hydrazone functionality also impacts arylboronic acid reactivity toward diols and reactive oxygen and nitrogen species (ROS/RNS). Untangling the communication between C=N linked functionalities and arylboronic acids has revealed a powerful and tunable motif for bioconjugation chemistries and other applications in chemical biology. Here, we survey the applications of iminoboronates and diazaborines in these fields with an eye toward understanding their utility as a function of neighboring group effects.